IL-18重组体联合HBVS基因核酸疫苗免疫小鼠的实验

Immune response induced in mice by codelivery of interleukin-18 recombinant and HBV S gene DNA vaccine

目的 研究IL 18重组体对HBVS基因核酸疫苗诱导小鼠产生特异性体液免疫和细胞免疫反应的影响 ,以探求HBV核酸疫苗免疫预防和治疗的新策略。方法 将 pcDNA3 S单独或联合pcDNA3 18免疫Balb/c小鼠 ,检测特异性体液免疫和细胞毒性T淋巴细胞 (CTL)反应 ,并作HBsAg特异性淋巴细胞增殖试验和特异性细胞因子诱导试验。结果 与pcDNA3 S免疫组比较 ,pcDNA3 18和pcDNA3 S联合免疫组小鼠的抗 HBs水平略高 ,但差异无显著性 (P >0 .0 5 )。特异性CTL活性显著升高 (P <0 .0 5 )。免疫小鼠的脾细胞体外经特异性抗原HBsAg刺激后 ,联合免疫组脾细胞上清液中IFN γ水平显著升高 (P <0 .0 5 ) ,IL 4水平差异无显著性 (P >0 .0 5 ) ,联合免疫组特异性HBsAg作用后脾细胞的刺激指数 (SI)高于 pcDNA3 S免疫组 ,但差异无显著性 (P >0 .0 5 )。结论 IL 18重组体联合HBVS基因核酸疫苗免疫小鼠 ,可促进机体诱导特异性TH1细胞和CTL细胞反应 ,增强机体的特异性细胞免疫功能 ,IL

Objective To investigate the effect of interleukin 18(IL 18)on immune response induced by plasmid encoding hepatitis B virus surface antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines. Methods Balb/c mice were immunized with pcDNA3 S alone or co immunized with pcDNA3 18 and pcDNA3 S.Their sera were collected for analyzing anti HBsAg antibody by ELISA and splenocytes were isolated for defecting specific CTL response. HBsAg specific lymphocyte proliferation test and specific cytokine level were also assayed in vitro . Results The anti HBsAg antibody level of mice co immunized with pcDNA3 18 and pcDNA3 S was slightly higher than that of mice immunized with pcDNA3 S alone, but there was no significant difference (P >0.05). Compared with mice injected with pcDNA3 S alone, the specific CTL cytotoxity activity of mice immunized with pcDNA3 18 and pcDNA3 S was significantly enhanced ( P <0.05) and the level of IFN γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated ( P <0.05) while the level of IL 4 did not change significantly ( P >0.05). The stimulatory index (SI) of splenocytes stimulated with HBsAg in co immunized group was slightly elevated compared with mice immunized with pcDNA3 S alone,but therewas no significant difference( P >0.05). Conclusions The plasmid encoding IL 18 together with HBV S gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response elicited in mice, hence IL 18 is a promising immune adjuvant.